Abstract
A large subset of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with HPV infection and has better outcome than non-viral-related tumors. Various malignancies also carry a role for TLRs, key activators of inflammation and innate immunity. We examined the expression of TLRs in OPSCC, and their association with HPV status and treatment outcome. TLR 5, 7, 9, and p16 were studied by immunohistochemistry and HPV status was detected with in situ hybridization in 202 tumors of consecutively treated OPSCC patients using tissue microarray method. The relations between TLR expression and HPV status, p16 expression, clinicopathological factors, and survival were analyzed. TLR 5, 7, and 9 expression patterns differed between HPV-positive and -negative tumors, and they were statistically significantly associated with history of smoking, heavy drinking, tumor site, grade, size (T), metastasis (N), and stage. Moreover, in HPV-positive tumors the expression of TLR 5 and 7 correlated with tumor recurrence. After adjustment, among HPV-positive OPSCC patients, high TLR 5 and low TLR 7 expression were associated with poor disease-specific survival. Our results indicate that TLR 5 and 7 may have a role in the prognostication of HPV-positive OPSCC, however, further studies are needed to clarify the comprehensive role of these TLRs in OPSCC.
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Abbreviations
- CI:
-
Confidence interval
- CRT:
-
Chemoradiotherapy
- DSS:
-
Disease-specific survival
- HR:
-
Hazard ratio
- ISH:
-
In situ hybridization
- OPSCC:
-
Oropharyngeal squamous cell carcinoma
- RFS:
-
Recurrence-free survival
- RT:
-
Radiotherapy
- SCC:
-
Squamous cell carcinoma
- Sx:
-
Surgery
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Acknowledgements
We thank Mrs. Elina Aspiala and Mrs. Päivi Peltokangas for technical assistance and Mr. Tero Vahlberg for statistical advice. This work was supported by the Orion Farmos Foundation, the Research Foundation of Finnish Otolaryngological Association, the Sigrid Jusélius Foundation, and the Finnish Dentist Association Apollonia.
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Jouhi, L., Mohamed, H., Mäkitie, A. et al. Toll-like receptor 5 and 7 expression may impact prognosis of HPV-positive oropharyngeal squamous cell carcinoma patients. Cancer Immunol Immunother 66, 1619–1629 (2017). https://doi.org/10.1007/s00262-017-2054-3
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DOI: https://doi.org/10.1007/s00262-017-2054-3